Rational design of oral delivery nanosystems for hypoglycemic peptides

Hypoglycemic peptides have exhibited great clinical benefits for diabetics and body weight control due to their high activity, high specificity, and low toxicity. However, frequent subcutaneous injection of hypoglycemic peptides is likely to trigger infections and adverse reactions. Oral administration is an ideal route for hypoglycemic peptides, but confronting a formidable challenge of poor oral bioavailability. The promising solution to solving this problem is to use nano drug delivery systems (NDDS). There are a series of biological barriers against effective delivery of peptide drugs including the mucus and epithelial barriers, which must be considered for rational design of oral NDDS. In this review, the therapeutic application of hypoglycemic peptides is introduced and the barriers restricting the delivery efficiency of oral NDDS are analyzed and discussed. We propose a six-step AMEIEB delivery cascade as a guideline for designing efficient oral NDDS of hypoglycemic peptides. And some specific considerations of how to improve delivery efficiency at each barrier are highlighted. The advances for overcoming these barriers and the recent delivery strategies are summarized.